Edinburgh Research Explorer

Computational design of probes to detect bacterial genomes by multivalent binding

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Accepted author manuscript, 3.01 MB, PDF document

    Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Original languageEnglish
Article number201918274
JournalProceedings of the National Academy of Sciences of the United States of America
DOIs
Publication statusPublished - 2 Apr 2020

Abstract

Rapid methods for diagnosis of bacterial infections are urgently needed to reduce inappropriate use of antibiotics, which contributes to antimicrobial resistance. In many rapid diagnostic methods, DNA oligonucleotide probes, attached to a surface, bind to specific nucleotide sequences in the DNA of a target pathogen. Typically, each probe binds to a single target sequence, i.e., target-probe binding is monovalent. Here we show using computer simulations that the detection sensitivity and specificity can be improved by designing
probes that bind multivalently to the entire length of the pathogen genomic DNA, such that a given probe binds to multiple sites along the target DNA. Our results suggest that multivalent targeting of long pieces of genomic DNA can allow highly sensitive and selective binding of the target DNA, even if competing DNA in the sample also contains binding sites for the same probe sequences. Our results are robust to mild fragmentation of the bacterial genome. Our conclusions may also be relevant for DNA detection in other fields, such as
disease diagnostics more broadly, environmental management and
food safety.

Download statistics

No data available

ID: 137619965